TH-AB-209-05: Validating Hemoglobin Saturation and Dissolved Oxygen in Tumors Using Photoacoustic Computed Tomographic Spectroscopic Imaging

Abstract

Purpose: Photoacoustic computed tomographic spectroscopy (PCT-S) provides intra-tumor measurements of oxygenation with high spatial resolution (0.2mm) and temporal fidelity (1–2 minutes) without the need for exogenous agents or ionizing radiation, thus providing a unique in vivo assay to measure SaO2 and investigate acute and chronic forms of hypoxia. The goal of this study is to validate in vivo SaO2 levels within tail artery of mice and the relationship between SaO2 and pO2 within subcutaneous breast tumors using PCT-S imaging, pulse oximetry and an OxyLite probe. Methods: A closed circuit phantom was fabricated to control blood oxygenation levels, where SaO2 was measured using a co-oximeter and pO2 using an Oxylite probe. Next, SaO2 levels within the tail arteries of mice (n=3) were measured using PCT-S and pulse oximetry while breathing high-to-low oxygen levels (6-cycles). Finally, PCT-S was used to measure SaO2 levels in MCF-7, MCF-7-VEGF165, and MDA-MB-231 xenograft breast tumors and compared to Oxylite pO2 levels values. Results: SaO2 and pO2 data obtained from the calibration phantom was fit to Hill's equation: aO2 levels between 88 and 52% demonstrated a linear relationship (r2=0.96) and a 3.2% uncertainty between PCT-S values relative to pulse oximetry. Scatter plots of localized PCT-S measured SaO2 and Oxylite pO2 levels in MCF-7/MCF-7-VEGF165 and MDA-MD-231 breast tumors were fit to Hill's equation: P50=17.2 and 20.7mmHg, and n=1.76 and 1.63. These results are consistent with sigmoidal form of Hill's equation, where the lower P50 value is indicative of an acidic tumor microenvironment. Conclusion: The results demonstrate photoacoustic imaging can be used to measure SaO2 cycling and intra-tumor oxygenation, and provides a powerful in vivo assay to investigate the role of hypoxia in radiation, anti-angiogenic, and immunotherapies.